Meperidine clearance

Meperidine readily passes the placenta into the fetus. However, respiratory depression in the newborn has not been observed, and meperidine clearance in the newborn is rapid in that it does not rely upon conjugation to glucuronides. Meperidine, unlike morphine, has not been associated with prolongation of labor conversely, it increases uterine contractions. 

Pond SM, Kretschzmar KM. Effect of phenytoin on meperidine clearance and normeperidine formation. Clin Pharmacol Ther 1981 30(5) 680-6. 

Like morphine, meperidine has an active metabolite, normeperidine, formed by A-demethylation of meperidine. Normeperidine is not analgesic but is a proconvulsant and a hallucinogenic agent. For this reason, meperidine use in patients with renal or fiver insufficiency is contraindicated because of the decreased clearance of the drug and its metabolite. Convulsant activity has been documented in elderly patients given meperidine and in patients using PCA who have decreased renal function. 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Chlorpromazine increases the respiratory-depressant effects of meperidine, as do tricyclic antidepressants this is not true of diazepam. Concurrent administration of drugs such as promethazine or chlorpromazine also may greatly enhance meperidine-induced sedation without slowing clearance of the drug. Treatment with phenobar-bital or phenytoin increases systemic clearance and decreases oral bioavailability of meperidine this is associated with an elevation of the concentration of normeperidine in plasma. As with morphine, concomitant administration of an amphetamine has been reported to enhance the analgesic effects of meperidine and its congeners while counteracting sedation. 

Concurrent administration of drugs such as promethazine or chlorpromazine may greatly enhance meperidine-induced sedation without slowing clearance of the drug. 

IMPAIRED HEPATIC CLEARANCE OF DRUGS The effect of liver disease on the hepatic biotransformation of drugs cannot be predicted from any measure of hepatic function. Thus, even though the metabolism of some drugs is decreased with impaired hepatic function, there is no quantitative basis for dose adjustment other than assessment of the clinical response and plasma concentration. The oral bioavailability of drugs with extensive first-pass hepatic clearance (e.g., morphine, meperidine, midazolam, and nifedipine) may be increased in liver disease. 

The elimination half-life of the drug is between 3-4 hours, but it may be simply doubled in patients with the liver malfunction. It has been observed that acidification of the urine may on one hand increase the clearance of meperidine, whereas on the other it may retard the clearance of the toxic metabolite normeperidine. 

The elimination half-life of meperidine is 3 to 4 hours, and it can double in patients with liver disease. Acidification of the urine will cause enhanced clearance of meperidine, but there is a lesser effect on the clearance of the toxic metabolite normeperidine. 

Urinary methadone clearance is increased if the urine is made acid (e.g. by giving ammonium chloride) and reduced if it is made alkaline (e.g. by giving sodium bicarbonate). The urinary clearance of dextropropoxyphene (propoxyphene) and pethidine (meperidine) may also be increased by acidification of the urine. 

After oral administration, the levels of normeperidine are increased compared to systemic administration. In hepatic disease, the reduced hepatic clearance of meperidine results in increased absorption necessitating a reduction in dose. Following intramuscular administration of meperidine, the elimination half-life (f P) is 3.6 hours (3.1-4.1 hours). Intramuscular absorption is highly variable with a two-fold variation in blood levels in the same patient and a wider five fold intra-patient variability. The l P is 111.4 hours in cirrhotic patients (range 8.3-18.7), but the levels of normeperidine are reduced. The elimination half-life of meperidine and normeperidine are prolonged in patients with renal failure. The l P elimination half-life of normeperidine is anywhere from 14-21 h to 24-48 h and as long as 34 h in renal failure [3]. 

Approximately 50% of oral meperidine is absorbed into the systemic circulation (range 41 to 61%). After oral administration the onset of analgesia is within 15 minutes and peak effects occur in 60-90 minutes [1,3]. In hepatic disease, with reduced hepatic clearance, the absorption of meperidine is increased from the gastrointestinal tract, necessitating a reduced dose. 

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